Advances in Alzheimer's Disease Treatments: A Dual Approach

INmune Bio has submitted the results of its phase 2 MINDFuL trial for XPro1595, a selective soluble tumor necrosis factor (TNF) neutralizer, to the journal npj Dementia. The trial, conducted across 35 centers in eight countries, aimed to evaluate the safety and efficacy of XPro in patients aged 50 to 85 with early Alzheimer's disease (AD) and signs of inflammation. Participants received weekly subcutaneous injections of either XPro1595 or a placebo for 24 weeks. While the trial did not meet its primary endpoint in the overall population, promising results were observed in a subgroup with both amyloid pathology and high inflammatory biomarkers, referred to as the ADi population.

Psychiatric TimesScienceAlertEuropean Commission approves Lilly’s Kisunla for treatment of early Alzheimer’s patientsLeqembi approved for use in AustraliaLilly’s early Alzheimer’s disease treatment approved in the EULeqembi wins NMPA nod for once-monthly IV dosing in early Alzheimer’s patientsNewsweek

CJ Barnum, VP of Neuroscience at INmune Bio, noted the trial's results indicate potential therapeutic value for XPro, particularly in targeting neuroinflammation. The treatment demonstrated a favorable safety profile, with no amyloid-related imaging abnormalities, a common side effect of amyloid-targeting therapies. David Moss, CEO of INmune Bio, expressed optimism about the upcoming discussions with regulatory authorities, including the FDA, EMA, and MHRA, anticipating feedback in early 2026.

Psychiatric Times

In parallel, Eli Lilly's Kisunla (donanemab) has received marketing authorization from the European Commission for treating early symptomatic Alzheimer's disease. This therapy targets amyloid plaques, which are associated with cognitive decline. Clinical trials, including the phase 3 TRAILBLAZER-ALZ 2 study, demonstrated that Kisunla significantly slowed cognitive and functional decline in patients with mild cognitive impairment and confirmed amyloid pathology.

European Commission approves Lilly’s Kisunla for treatment of early Alzheimer’s patientsLilly’s early Alzheimer’s disease treatment approved in the EULeqembi wins NMPA nod for once-monthly IV dosing in early Alzheimer’s patientsScienceAlertLeqembi approved for use in AustraliaPsychiatric Times

Similarly, lecanemab (Leqembi) has been approved in Australia for early Alzheimer's patients. This monoclonal antibody therapy also targets amyloid buildup, showing a 27% reduction in disease progression over 18 months in clinical trials. However, both therapies are associated with potential side effects, including amyloid-related imaging abnormalities (ARIA), which can lead to serious complications.

ScienceAlertEuropean Commission approves Lilly’s Kisunla for treatment of early Alzheimer’s patientsLeqembi wins NMPA nod for once-monthly IV dosing in early Alzheimer’s patientsLeqembi approved for use in Australia

Despite the advancements, there are concerns regarding the accessibility and safety of these treatments. Dementia Australia CEO Professor Tanya Buchanan emphasized the need for equitable access to new therapies, cautioning that patients must be informed about potential side effects. Critics argue that the healthcare system may not be prepared for the influx of early Alzheimer's diagnoses, which could overwhelm existing resources.

Leqembi approved for use in Australia

Additionally, the ethical implications of early detection and treatment are debated. Some experts advocate for early diagnosis to empower patients with knowledge and options, while others caution against the anxiety and stigma that may accompany such diagnoses.

Technology Networks

The recent developments in Alzheimer's disease treatments, including XPro1595, Kisunla, and lecanemab, represent a significant shift towards targeting both neuroinflammation and amyloid pathology. As research continues to evolve, the focus on metabolic dysfunction in brain cells may open new avenues for therapeutic strategies. However, the challenges of accessibility, safety, and ethical considerations remain critical as the medical community navigates this complex landscape.

ScienceAlert